Betamethasone Dipropionate

1 INDICATIONS AND USAGE Betamethasone dipropionate lotion (augmented), 0.05% is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 13 years of age or older. Betamethasone dipropionate lotion (augmented), 0.05% is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 13 years of age and older. ( 1 )

2 DOSAGE AND ADMINISTRATION Apply a few drops of betamethasone dipropionate lotion (augmented), 0.05% to the affected skin areas once or twice daily and massage lightly until the lotion disappears. Therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Betamethasone dipropionate lotion (augmented), 0.05% is a super-high-potency topical corticosteroid. Treatment with betamethasone dipropionate lotion (augmented), 0.05% should be limited to 2 consecutive weeks and amounts should not exceed 50 mL per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis [see Warnings and Precautions (5.1) ] . Betamethasone dipropionate lotion (augmented), 0.05% should not be used with occlusive dressings unless directed by a physician. Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. Avoid contact with eyes. Wash hands after each application. Betamethasone dipropionate lotion (augmented), 0.05% is for topical use only. It is not for oral, ophthalmic, or intravaginal use. • Apply a few drops to the affected skin areas once or twice daily and massage lightly until the lotion disappears.( 2 ) • Discontinue therapy when control is achieved. ( 2 ) • Limit therapy to no more than 2 consecutive weeks. ( 2 ) • Use no more than 50 mL per week. ( 2 ) • Do not use with occlusive dressings unless directed by a physician. ( 2 ) • Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. ( 2 ) • Not for oral, ophthalmic, or intravaginal use. ( 2 )

5 WARNINGS AND PRECAUTIONS • Effects on endocrine system: Betamethasone dipropionate lotion (augmented), 0.05% can cause reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency during and after withdrawal of treatment. Risk factor(s) include the use of high-potency topical corticosteroids, use over a large surface area or to areas under occlusion, prolonged use, altered skin barrier, liver failure, and use in pediatric patients. Modify use should HPA axis suppression develop. ( 5.1 , 8.4 ) • Ophthalmic Adverse Reactions: Betamethasone dipropionate lotion (augmented), 0.05% may increase the risk of cataracts and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist for evaluation. ( 5.2 ) 5.1 Effects on Endocrine System Betamethasone dipropionate lotion (augmented), 0.05% can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during treatment or after withdrawal of treatment. Factors that predispose to HPA axis suppression include the use of high-potency steroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age. Evaluation for HPA axis suppression may be done by using the adrenocorticotropic hormone (ACTH) stimulation test. In a trial evaluating the effects of betamethasone dipropionate lotion (augmented), 0.05% on the HPA axis, betamethasone dipropionate lotion (augmented), 0.05% was applied once daily at 7 mL per day for 21 days to diseased scalp and body skin in subjects with scalp psoriasis, betamethasone dipropionate lotion (augmented), 0.05% was shown to lower plasma cortisol levels below normal limits in 2 out of 11 subjects. HPA axis suppression in these subjects was transient and returned to normal within a week. In one of these subjects, plasma cortisol levels returned to normal while treatment continued. If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids. Cushing's syndrome and hyperglycemia may also occur with topical corticosteroids. These events are rare and generally occur after prolonged exposure to excessively large doses, especially of high-potency topical corticosteroids. Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface to body mass ratios [see Use in Specific Populations (8.4) ]. 5.2 Ophthalmic Adverse Reactions Use of topical corticosteroids, including betamethasone dipropionate lotion (augmented), 0.05%, may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported postmarketing with the use of topical corticosteroid products, including betamethasone dipropionate lotion (augmented), 0.05% [see Adverse Reactions (6.2) ] . Avoid contact of betamethasone dipropionate lotion (augmented), 0.05% with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation. 5.3 Allergic Contact Dermatitis Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Such an observation should be corroborated with appropriate diagnostic patch testing. If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted.

4 CONTRAINDICATIONS Betamethasone dipropionate lotion (augmented), 0.05% is contraindicated in patients who are hypersensitive to betamethasone dipropionate, to other corticosteroids, or to any ingredient in this preparation. • Hypersensitivity to any component of this medicine. ( 4 )

8.1 Pregnancy Risk Summary There are no available data on betamethasone dipropionate lotion (augmented), 0.05% use in pregnant women to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Observational studies suggest an increased risk of low birthweight infants with the use of greater than 300 grams of potent or very potent topical corticosteroid during a pregnancy. Advise pregnant women that betamethasone dipropionate lotion (augmented), 0.05% may increase the risk of having a low birthweight infant and to use betamethasone dipropionate lotion (augmented), 0.05% on the smallest area of skin and for the shortest duration possible. In animal reproduction studies, increased malformations, including umbilical hernias, cephalocele, and cleft palate, were observed after intramuscular administration of betamethasone dipropionate to pregnant rabbits. The available data do not allow the calculation of relevant comparisons between the systemic exposure of betamethasone dipropionate in animal studies to the systemic exposure that would be expected in humans after topical use of betamethasone dipropionate lotion (augmented), 0.05% (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Betamethasone dipropionate has been shown to cause malformations in rabbits when given by the intramuscular route at doses of 0.05 mg/kg. The abnormalities observed included umbilical hernias, cephalocele, and cleft palate.

6 ADVERSE REACTIONS Most common adverse reactions (<1%) are: erythema, folliculitis, pruritus, and vesiculation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fougera Pharmaceuticals Inc. at 1-800-645-9833 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In controlled clinical trials, adverse reactions associated with the use of betamethasone dipropionate lotion (augmented), 0.05% reported at a frequency of less than 1% included erythema, folliculitis, pruritus, and vesiculation. 6.2 Postmarketing Experience Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Postmarketing reports for local adverse reactions to topical corticosteroids may also include: skin atrophy, striae, telangiectasias, burning, irritation, dryness, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, hypertrichosis, and miliaria. Hypersensitivity reactions, consisting of predominantly skin signs and symptoms, e.g., contact dermatitis, pruritus, bullous dermatitis, and erythematous rash have been reported. Ophthalmic adverse reactions of cataracts, glaucoma, increased intraocular pressure, and central serous chorioretinopathy have been reported with the use of topical corticosteroids, including topical betamethasone products.